Antiglucocorticoid activity of androgens in rat thymus lymphocytes

The potent androgens testosterone and 5 alpha-dihydrotestosterone, but not the inactive androgens etiocholanolone and androsterone, display antiglucocorticoid activity in rat thymus-derived lymphocytes. At a concentration of 10(-5) M, the potent androgens markedly lower the in vitro cytolytic response of isolated thymic lymphocytes to 10(-8) M dexamethasone. AT 2.5 X 10(-5) M, these androgens completely prevent the inhibition produced by 5 X 10(-8) M dexamethasone on 2-deoxyglucose uptake and uridine uptake and incorporation in isolated thymic lymphocytes. In the cytosol fraction obtained from rat thymus homogenate, the active androgens competitively inhibit the binding of [3H]dexamethasone to glucocorticoid-specific receptors with Ki values of 1.2 X 10(-6) and 2.5 X 10(-6) M for testosterone and 5 alpha-dihydrotestosterone, respectively. Thymus-derived lymphocytes and nuclei isolated from these cells exhibit binding of [3H]dexamethasone. The bound dexamethasone is avidly displaced by an excess of nonradioactive dexamethasone as well as by nonradioactive testosterone or 5 alpha-dihydrotestosterone. In contrast to their antiglucocorticoid activity in vitro, these androgens fail to elicit antiglucocorticoid activity when administered in vivo. This work shows that androgens are potent antiglucocorticoids in vitro due to competition with the active glucocorticoid on binding to cytoplasmic and nuclear receptor sites.